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The study included 8, 252 participants with a mean age of 57.3 ± 9.0 years, and 36.97% were men. The mean serum uric acid level was 350.97 ± 88.42 μmol/L in men and 267.21 ± 78.24 μmol/L in women, respectively. The prevalence rates of obesity, hypertension, and dyslipidemia were 5.87% (5.67% in men and 5.98% in women), 55.84% (59.39% in men and 53.76% in women), and 37.59% (40.28% in men and 36.01% in women). A total of 6.81% of the participants reported having CVDs, 423 (5.50%) had an increased estimated 10-year Framingham risk for coronary heart disease, and 3, 050 (39.66%) had an increased estimated 10-year risk for a first hard ASCVD event.
The basic characteristics of the participants according to serum uric acid quartiles in men and women are shown in Table 1. Men and women with increased serum uric acid levels tended to be older, obese, and had significantly higher levels of blood pressure, total cholesterol, triglycerides, LDL-C, HOMA-IR, waist circumference, and a lower estimated glomerular filtration rate and HDL-C levels (all P < 0.001). Men with a higher serum uric acid level had higher proportions of current smokers and current drinkers.
Table 1. Characteristics of the Study Populations according to Serum Uric Acid Quartiles (N = 8, 252)
Characteristics UA (μmol/L) P for Trend Q1 Q2 Q3 Q4 Men Number/percentage, % 764 (25.0%) 762 (25.0%) 763 (25.0%) 762 (25.0%) Uric acid, μmol/L 258.5 (232.3-278.9) 319.8 (307.8-332.2) 371.2 (359.1-387.7) 451.5 (424.8-495.1) < 0.0001 Age, years 58.3 ± 9.2 57.0 ± 9.2 57.6 ± 9.1 58.4 ± 9.6 0.0081 High school education or above, % 175 (22.9%) 201 (26.4%) 193 (25.3%) 198 (26.0%) 0.72 Current smoker, % 454 (60.0%) 419 (55.7%) 426 (56.4%) 367 (48.9%) 0.0001 Current drinker, % 157 (20.8%) 188 (25.3%) 207 (27.5%) 223 (30.1%) 0.0001 Physically active during leisure time, % 105 (13.7%) 94 (12.3%) 104 (13.6%) 106 (13.9%) 0.93 BMI, kg/m2 23.9 ± 2.8 24.8 ± 3.0 25.5 ± 3.0 26.2 ± 3.0 < 0.0001 Waist circumference, cm 81.1 ± 7.7 84.0 ± 8.3 86.2 ± 8.0 88.4 ± 8.1 < 0.0001 SBP, mmHg 136.7 ± 18.4 138.6 ± 18.2 140.3 ± 18.6 141.1 ± 17.8 < 0.0001 DBP, mmHg 82.0 ± 10.3 84.0 ± 9.9 85.3 ± 10.0 86.0 ± 10.0 < 0.0001 FBG, mmol/L 5.1 ± 0.6 5.1 ± 0.6 5.1 ± 0.6 5.2 ± 0.6 0.0008 PBG, mmol/L 6.0 ± 1.8 6.3 ± 1.8 6.4 ± 1.8 6.9 ± 1.8 < 0.0001 HbA1c, % 5.5 (5.3-5.7) 5.5 (5.3-5.7) 5.5 (5.3-5.7) 5.6 (5.3-5.8) 0.0072 Total cholesterol, mg/dL 4.88 ± 0.82 5.08 ± 0.96 5.11 ± 0.84 5.23 ± 0.97 < 0.0001 Triglyceride, mg/dL 1.03 (0.77-1.41) 1.25 (0.95-1.73) 1.41 (1.02-1.98) 1.73 (1.22-2.50) < 0.0001 HDL-C, mg/dL 1.33 ± 0.31 1.25 ± 0.30 1.22 ± 0.29 1.19 ± 0.29 < 0.0001 LDL-C, mg/dL 2.85 ± 0.69 3.04 ± 0.76 3.06 ± 0.75 3.11 ± 0.86 < 0.0001 HOMA-IR 0.97 (0.56-1.38) 1.23 (0.83-1.81) 1.49 (0.96-2.14) 1.67 (1.10-2.44) < 0.0001 Women Number/percentage % 1301 (25.0%) 1300 (25.0%) 1301 (25.0%) 1299 (25.0%) Uric acid, μmol/L 183.0 (160.8-197.8) 232.30 (222.05-243.45) 277.4 (265.8-289.9) 347.8 (324.5-390.2) < 0.0001 Age, years 54.6 ± 8.8 56.1 ± 8.3 57.5 ± 8.8 59.7 ± 8.5 < 0.0001 High school education or above, % 295 (22.7%) 284 (21.9%) 281 (21.6%) 225 (17.3%) 0.0034 Current smoker, % 5 (0.4%) 4 (0.3%) 6 (0.5%) 9 (0.7%) 0.50 Current drinker, % 7 (0.6%) 9 (0.7%) 15 (1.2%) 10 (0.8%) 0.32 Physically active during leisure time, % 161 (12.4%) 203 (15.6%) 210 (16.1%) 209 (16.1%) 0.02 BMI, kg/m2 23.6 ± 3.0 24.4 ± 2.9 25.1 ± 3.2 26.1 ± 3.3 < 0.0001 Waist circumference, cm 76.5 ± 8.0 79.0 ± 7.4 80.9 ± 8.2 83.7 ± 8.3 < 0.0001 SBP, mmHg 133.6 ± 18.7 137.4 ± 19.4 139.5 ± 20.3 145.0 ± 20.3 < 0.0001 DBP, mmHg 79.6 ± 9.9 81.0 ± 9.9 82.0 ± 10.0 83.6 ± 10.3 < 0.0001 FBG, mmol/L 5.0 ± 0.5 5.1 ± 0.5 5.1 ± 0.6 5.2 ± 0.6 < 0.0001 PBG, mmol/L 6.4 ± 1.5 6.7 ± 1.6 6.9 ± 1.7 7.3 ± 1.7 < 0.0001 HbA1c, % 5.5 (5.3-5.7) 5.5 (5.3-5.7) 5.6 (5.4-5.8) 5.6 (5.4-5.9) < 0.0001 Total cholesterol, mg/dL 5.24 ± 0.96 5.41 ± 0.90 5.45 ± 1.03 5.67 ± 1.10 < 0.0001 Triglyceride, mg/dL 1.03 (0.78-1.41) 1.24 (0.93-1.74) 1.39 (1.03-1.90) 1.66 (1.25-2.36) < 0.0001 HDL-C, mg/dL 1.49 ± 0.33 1.41 ± 0.30 1.36 ± 0.30 1.30 ± 0.29 < 0.0001 LDL-C, mg/dL 3.08 ± 0.83 3.24 ± 0.80 3.29 ± 0.91 3.45 ± 0.92 < 0.0001 HOMA-IR 1.28 (0.89-1.73) 1.46 (1.02-2.01) 1.68 (1.17-2.38) 2.02 (1.42-2.92) < 0.0001 Note. UA, uric acid; BMI, body mass index; SBP, systolic blood pressure; DBP, diastolic blood pressure; FPG, fasting plasma glucose; PBG, postprandial blood glucose; HbA1c, hemoglobin A1; LDL-C, low density lipoprotein cholesterol; HDL-C, high density lipoprotein cholesterol. A multivariate logistic regression analysis indicated that increased serum uric acid level was associated with an increased risk of prevalent obesity, hypertension, and dyslipidemia in men and women (all P for trend < 0.001; Table 2).
Table 2. Association between Serum Uric Acid Concentrations and Cardiovascular Risk Factors in Middle-aged and Elderly Chinese Adults without Diabetes (N = 8, 252)
Variables UA (μmol/L) P for Trend Q1 Q2 Q3 Q4 Obesity Men (n = 3, 051) Case percentage (%) 19 (2.49%) 37 (4.86%) 48 (6.29%) 69 (9.06%) < 0.0001 Age-adjusted OR (95% CI) 1.00 1.98 (1.13-3.47) 2.62 (1.52-4.50) 3.91 (2.33-6.56) < 0.0001 Multivariate adjusted OR (95% CI)* 1.00 1.88 (1.06-3.33) 2.34 (1.35-4.06) 3.42 (2.01-5.81) < 0.0001 Women (n = 5, 201) Case percentage (%) 34 (2.61%) 46 (3.54%) 76 (5.84%) 155 (11.93%) < 0.0001 Age-adjusted OR (95% CI) 1.00 1.36 (0.87-2.14) 2.29 (1.52-3.47) 4.98 (3.38-7.32) < 0.0001 Multivariate adjusted OR (95% CI)* 1.00 1.34 (0.85-2.12) 2.04 (1.33-3.13) 4.18 (2.80-6.24) < 0.0001 Hypertension Men (n = 3, 051) Case percentage (%) 390 (51.05%) 439 (57.61%) 464 (60.81%) 519 (68.11%) < 0.0001 Age-adjusted OR (95% CI) 1.00 1.44 (1.17-1.78) 1.60 (1.30-1.97) 2.16 (1.74-2.67) < 0.0001 Multivariate adjusted OR (95% CI)** 1.00 1.15 (0.92-1.43) 1.13 (0.90-1.41) 1.29 (1.02-1.63) 0.04 Women (n = 5, 201) Case percentage (%) 515 (39.58%) 640 (49.23%) 721 (55.42%) 920 (70.82%) < 0.0001 Age-adjusted OR (95% CI) 1.00 1.37 (1.17-1.62) 2.86 (2.42-3.40) 1.07 (1.06-1.08) < 0.0001 Multivariate adjusted OR (95% CI)** 1.00 1.16 (0.98-1.38) 1.30 (1.09-1.54) 1.96 (1.63-2.36) < 0.0001 Dyslipidemia Men (n = 3, 051) Case percentage (%) 188 (24.61%) 279 (36.61%) 330 (43.25%) 432 (56.69%) < 0.0001 Age-adjusted OR (95% CI) 1.00 1.72 (1.38-2.15) 2.32 (1.86-2.89) 4.11 (3.29-5.12) < 0.0001 Multivariate adjusted OR (95% CI)*** 1.00 1.49 (1.18-1.88) 1.89 (1.50-2.38) 3.16 (2.50-3.99) < 0.0001 Women (n = 5, 201) Case percentage (%) 273 (20.98%) 420 (32.31%) 491 (37.74%) 689 (53.04%) < 0.0001 Age-adjusted OR (95% CI) 1.00 1.75 (1.47-2.09) 2.17 (1.82-2.58) 3.88 (3.25-4.62) < 0.0001 Multivariate adjusted OR (95% CI)*** 1.00 1.66 (1.39-2.00) 1.99 (1.66-2.38) 3.23 (2.68-3.88) < 0.0001 Note. OR, odds ratio; CI, confidence interval; UA, uric acid; BMI, body mass index; *Multivariable model adjusted for age, education attainment, current smoking status, current alcohol consumption, MET-min/week, HbA1c, SBP, total cholesterol. **Multivariable model adjusted for age, education attainment, current smoking status, current alcohol consumption, MET-min/week, BMI, HbA1c, total cholesterol. ***Multivariable model adjusted for age, education attainment, current smoking status, current alcohol consumption, MET-min/week, BMI, HbA1c, SBP. Significant data in bold. The association between serum uric acid level and prevalent CVD was further evaluated. A total of 221 (7.24%) men and 341 (6.56%) women had a history of CVD, including 141 (4.64%) with coronary heart disease, 10 (0.33%) with a myocardial infarction, and 80 (2.63%) with stroke in men, and 249 (4.82%) with coronary heart disease, three (0.06%) with myocardial infarction, and 101 (1.92%) with stroke in women. Elevated serum uric acid was associated with an increased risk of prevalent CVDs. The prevalence numbers of self-reported CVDs were 42 (5.50%), 45 (5.91%), 60 (7.86%), and 74 (9.71%) in men and 59 (4.53%), 78 (6.00%), 80 (6.15%), and 124 (9.55%) in women across quartiles of serum uric acid (all P for trend < 0.001). Multivariate adjusted ORs (95% CI) of prevalent cardiovascular disease risk associated with serum uric acid were 1.00, 1.16 (0.74-1.82), 1.51 (0.99-2.33), and 1.67 (1.09-2.55; P for trend < 0.001) for men, and 1.00, 1.21 (0.84-1.72), 1.13 (0.79-1.62), and 1.50 (1.06-2.12) (P for trend < 0.001) for women, respectively, Table 3.
Table 3. Association between Serum Uric Acid Levels and Cardiovascular Disease in Middle-aged and Elderly Chinese Adults without Diabetes
Variables UA (μmol/L) P for Trend Q1 Q2 Q3 Q4 Cardiovascular diseases (n = 8, 252) Men (n = 3, 051) Case percentage (%) 42 (5.50%) 45 (5.91%) 60 (7.86%) 74 (9.71%) 0.0003 Age-adjusted OR (95% CI) 1.00 1.22 (0.78-1.89) 1.60 (1.06-2.44) 1.85 (1.24-2.77) 0.001 Multivariate adjusted OR (95% CI)† 1.00 1.16 (0.74-1.82) 1.51 (0.99-2.33) 1.67 (1.09-2.55) 0.009 Women (n = 5, 201) Case percentage (%) 59 (4.53%) 78 (6.00%) 80 (6.15%) 124 (9.55%) Age-adjusted OR (95% CI) 1.00 1.25 (0.88-1.77) 1.14 (0.80-1.62) 1.61 (1.16-2.23) 0.007 Multivariate adjusted OR (95% CI)† 1.00 1.21 (0.84-1.72) 1.13 (0.79-1.62) 1.50 (1.06-2.12) 0.03 Framingham risk score > 20%††† (n = 7, 690) Men (n = 2, 830) Case percentage (%) 61 (8.45%) 78 (10.88%) 105 (14.94%) 132 (19.19%) < 0.0001 Age-adjusted OR (95% CI) 1.00 1.54 (1.10-2.18) 2.14 (1.54-2.98) 2.83 (2.01-3.98) < 0.0001 Multivariate adjusted OR (95% CI)† 1.00 1.39 (0.92-2.12) 2.05 (1.37-3.06) 3.00 (2.00-4.50) < 0.0001 Women (n = 4, 860) Case percentage (%) 6 (0.49%) 5 (0.42%) 7 (0.58%) 29 (2.39%) < 0.0001 Age-adjusted OR (95% CI) 1.00 0.39 (0.11-1.41) 1.07 (0.42-2.74) 4.73 (1.70-11.25) 0.0005 Multivariate adjusted OR (95% CI)† 1.00 0.44 (0.10-1.83) 1.01 (0.33-1.75) 2.95 (1.08-8.43) 0.01 ASCVD risk score ≥ 7.5%†† (n = 7, 690) Men (n = 2, 830) Case percentage (%) 484 (67.04%) 487 (67.92%) 511 (72.69%) 509 (73.98%) 0.0004 Age-adjusted OR (95% CI) 1.00 1.49 (1.11-2.00) 1.98 (1.46-2.69) 2.08 (1.52-2.84) < 0.0001 Multivariate adjusted OR (95% CI)† 1.00 1.52 (0.97-2.41) 1.87 (1.17-2.99) 1.93 (1.17-3.17) 0.005 Women (n = 4, 860) Case percentage (%) 171 (13.77%) 190 (15.55%) 287 (23.51%) 411 (34.98%) < 0.0001 Age-adjusted OR (95% CI) 1.00 1.41 (0.97-2.04) 2.62 (1.83-3.74) 5.40 (3.71-7.87) < 0.0001 Multivariate adjusted OR (95% CI)† 1.00 1.06 (0.58-1.91) 2.48 (1.39-4.42) 4.53 (2.57-7.98) < 0.0001 Note. OR, odds ratio; CI, confidence interval; CVD, cardiovascular diseases; ASCVD, atherosclerotic cardiovascular diseases; HOMA-IR, homeostasis model assessment of insulin resistance. †Multivariable model adjusted for age, education attainment, current smoking status, current alcohol consumption, MET-min/week, BMI, HbA1c, SBP, total cholesterol. ††Analysis was carried out in participants ages 40-79 years old, free of CVD and diabetes (N = 7, 690) and individuals with ASCVD score ≥ 7.5% were identified as at high risks for 10-year ASCVD. †††Analysis was carried out in participants ages 40-79 years old, free of CVD and diabetes (n = 7, 690), and Framingham risk score > 20% were identified as at high risks for 10-year coronary heart disease. Significant data in bold. The estimated 10-year Framingham risk for coronary heart disease and estimated 10-year risk for a first hard ASCVD event were further calculated in participants free of CVDs (n = 7, 690, Table 3; Figure 1). Men had a significantly higher risk according to the Framingham risk score and ASCVD than women. The mean Framingham risk score was 13.63% ± 7.27% in men and 3.33% ± 3.86% in women. There were 376 (13.29%) men and 47 (0.97%) women who had a 10-year Framingham risk for coronary heart disease > 20%. The mean ASCVD risk score was 13.92% ± 9.7% in men and 5.53% ± 6.78% in women. A total of 70.35% of men and 21.79% of women had ASCVD risk ≥ 7.5%.
Figure 1. Distribution of estimated 10-year risk for a first hard atherosclerotic cardiovascular diseases (ASCVD) event (A) and 10-year Framingham risk for coronary heart disease (B) in middle-aged and elderly Chinese adults without diabetes or CVD, stratified by sex and serum uric acid concentration groups (N = 7, 690).
As shown in Figure 1, the distribution of the two estimated risk scores was stratified by sex and serum uric acid level. Serum uric acid was associated with increased 10-year Framingham risk for coronary heart disease and the 10-year risk for ASCVD after multivariate adjustments (P for trend < 0.001; Table 3, Figure 1) in men and women. Multivariate adjusted ORs (95% CI) of the high Framingham risk associated with serum uric acid were: 1.00, 1.39 (0.92-2.12), 2.05 (1.37-3.06), and 3.00 (2.00-4.50) in men and 1.00, 0.44 (0.10-1.83), 1.01 (0.33-1.75), and 2.95 (1.08-8.43) in women. Multivariate adjusted ORs (95% CI) of the ASCVD risk associated with serum uric acid were 1.00, 1.52 (0.97-2.41), 1.87 (1.17-2.99), 1.93 (1.17-3.17) in men and 1.00, 1.06 (0.58-1.91), 2.48 (1.39-4.42), 4.53 (2.57-7.98) in women (Table 3).
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In the present cross-sectional study conducted among the middle-aged and elderly Chinese populations, we found that higher serum uric acid levels were significantly associated with an increased risk of prevalent cardiometabolic diseases, estimated from the 10-year Framingham risk for coronary heart disease and the 10-year risk for a first hard ASCVD event.
Our findings about the association between serum uric acid and cardiometabolic diseases are in accordance with previous studies[2, 6, 9, 15, 22]. In a restricted generalized study of 3, 073 highly selected middle-aged male participants without diabetes or metabolic syndrome, higher serum uric acid levels were significantly associated with an increased risk for hypertension[6]. However, data on the risks of 10-year Framingham risk for coronary heart disease or 10-year risk for ASCVD are limited, especially among female counterparts. In another small study of 581 elderly patients with type 2 diabetes, higher serum uric acid level independently predicted cardiovascular mortality, but the authors did not adjust for glycemic control[23]. In this respect, the effect of gender differences and HbA1c levels on serum uric acid concentration cannot be ignored[1]. In a large middle-aged and elderly Chinese population, Lai et al. reported that higher serum uric acid level was independently associated with a dose-response increased risk for coronary heart disease[15]. However, they did not exclude patients with diabetes, who have significantly lower urate levels, and they did not perform sex-specific analyses. Sex-specific analysis is needed when investigating the association between serum uric acid level and CVD risk, because serum uric acid level is higher in men than in women of all age groups[1]. In our study, we further explored the association between serum uric acid level and coronary heart disease risk factors. The highest quartile of serum uric acid was significantly associated with an increased risk of prevalent cardiovascular diseases, compared with the lowest uric acid quartile, and predicted cardiovascular risk in participants without obesity (Table S1, available at www.besjournal.com).
Table Table S1. Subgroup Analysis of the Association between Serum Uric Acid Levels and Cardiovascular Diseases in Middle-Aged and Elderly Chinese Adults without Diabetes
Variables UA (μmol/L) P for Trend Q1 Q2 Q3 Q4 Cardiovascular diseases (n = 8, 252) Age < 60 y (n = 5, 247) 40 (2.84%) 57 (4.07%) 36 (2.79%) 65 (5.66%) 0.002 Multivariate adjusted OR (95% CI)† 1.00 1.33 (0.87-2.02) 0.91 (0.57-1.45) 1.72 (1.12-2.66) 0.06 ≥ 60 y (n = 2, 641) 61 (9.28%) 66 (9.98%) 104 (13.42%) 133 (14.58%) 0.0001 Multivariate adjusted OR (95% CI)† 1.00 1.03 (0.71-1.49) 1.44 (1.02-2.02) 1.45 (1.03-2.04) 0.009 Obesity No (n = 7, 768) 97 (4.82%) 112 (5.66%) 127 (6.55%) 163 (8.87%) < 0.0001 Multivariate adjusted OR (95% CI)†† 1.00 1.13 (0.85-1.50) 1.22 (0.92-1.62) 1.43 (1.09-1.89) 0.009 Yes (n = 484) 4 (7.55%) 11 (13.25%) 13 (10.48%) 35 (15.63%) 0.07 Multivariate adjusted OR (95% CI)†† 1.00 2.05 (0.58-7.20) 1.53 (0.45-5.22) 2.13 (0.68-6.71) 0.29 Hypertension No (n = 3, 644) 33 (2.84%) 33 (3.36%) 30 (3.41%) 32 (5.14%) 0.01 Multivariate adjusted OR (95% CI)††† 1.00 1.12 (0.68-1.86) 1.13 (0.68-1.90) 1.68 (0.99-2.85) 0.08 Yes (n = 4, 608) 68 (7.51%) 90 (8.34%) 110 (9.28%) 166 (11.54%) 0.0003 Multivariate adjusted OR (95% CI)††† 1.00 1.16 (0.83-1.63) 1.18 (0.85-1.64) 1.28 (0.93-1.75) 0.15 Dyslipidemia No (n = 5, 150) 75 (4.68%) 73 (5.36%) 84 (6.76%) 89 (9.47%) < 0.0001 Multivariate adjusted OR (95% CI)†††† 1.00 1.09 (0.77-1.53) 1.27 (0.91-1.77) 1.56 (1.12-2.19) 0.006 Yes (n = 3, 102) 26 (5.64%) 50 (7.15%) 56 (6.82%) 109 (9.72%) 0.002 Multivariate adjusted OR (95% CI)†††† 1.00 1.27 (0.77-2.10) 1.10 (0.67-1.81) 1.28 (0.80-2.04) 0.45 Framingham risk score > 20% (n = 7, 690) Age < 60 y (n = 5, 049) 31 (2.27%) 41 (3.05%) 63 (5.03%) 51 (4.70%) < 0.0001 Multivariate adjusted OR (95% CI)† 1.00 0.96 (0.54-1.70) 1.75 (1.01-3.01) 1.25 (0.70-2.23) < 0.0001 ≥ 60 y (n = 2, 641) 36 (6.04%) 42 (7.06%) 49 (7.30%) 110 (14.12%) < 0.0001 Multivariate adjusted OR (95% CI)† 1.00 1.06 (0.63-1.79) 1.01 (0.61-1.66) 1.97 (1.23-3.15) 0.01 Obesity No (n = 7, 269) 64 (3.34%) 80 (4.28%) 105 (5.79%) 147 (8.78%) < 0.0001 Multivariate adjusted OR (95% CI)†† 1.00 1.32 (0.87-2.00) 1.59 (1.07-2.37) 2.12 (1.43-3.14) < 0.0001 Yes (n = 421) 3 (6.12%) 3 (4.17%) 7 (6.31%) 14 (7.41%) 0.23 Multivariate adjusted OR (95% CI)†† 1.00 0.59 (0.07-4.77) 0.89 (0.14-5.62) 1.13 (0.21-6.09) 0.62 Hypertension No (n = 3, 516) 9 (0.80%) 8 (0.84%) 17 (2.00%) 7 (1.19%) 0.05 Multivariate adjusted OR (95% CI)††† 1.00 0.82 (0.28-2.38) 1.49 (0.58-3.84) 0.71 (0.23-2.20) 0.92 Yes (n = 4, 174) 58 (6.93%) 75 (7.58%) 95 (8.84%) 154 (12.10%) < 0.0001 Multivariate adjusted OR (95% CI)††† 1.00 1.39 (0.90-2.17) 1.56 (1.02-2.38) 1.98 (1.31-3.00) 0.001 Dyslipidemia No (n = 4, 829) 28 (1.83%) 32 (2.48%) 32 (2.76%) 30 (3.53%) 0.01 Multivariate adjusted OR (95% CI)†††† 1.00 1.75 (0.95-3.20) 1.65 (0.90-3.04) 1.98 (1.04-3.77) 0.05 Yes (n = 2, 861) 39 (8.97%) 51 (7.86%) 80 (10.46%) 131 (12.94%) 0.001 Multivariate adjusted OR (95% CI)†††† 1.00 0.88 (0.50-1.54) 1.25 (0.74-2.10) 1.61 (0.97-2.66) 0.01 ASCVD risk score ≥ 7.5% (n = 7, 690) Age < 60 y (n = 5, 049) 204 (14.91%) 248 (18.45%) 279 (22.27%) 270 (24.91%) < 0.0001 Multivariate adjusted OR (95% CI)† 1.00 1.09 (0.81-1.47) 1.26 (0.94-1.70) 1.24 (0.91-1.69) 0.11 ≥ 60 y (n = 2, 641) 451 (75.67%) 429 (72.10%) 519 (77.35%) 650 (83.44%) < 0.0001 Multivariate adjusted OR (95% CI)† 1.00 0.77 (0.57-1.06) 1.00 (0.73-1.37) 1.43 (1.04-1.98) 0.007 Obesity No (n = 7, 269) 639 (33.21%) 644 (34.49%) 750 (41.37%) 825 (49.28%) < 0.0001 Multivariate adjusted OR (95% CI)†† 1.00 1.07 (0.82-1.40) 1.33 (1.02-1.73) 1.53 (1.17-2.00) 0.001 Yes (n = 421) 19 (38.78%) 33 (45.83%) 48 (43.24%) 95 (50.26%) 0.08 Multivariate adjusted OR (95% CI)†† 1.00 1.84 (0.57-5.94) 1.74 (0.57-5.28) 1.19 (0.41-3.43) 0.09 Hypertension No (n = 3, 516) 230 (20.41%) 203 (21.37%) 215 (25.32%) 155 (26.27%) 0.001 Multivariate adjusted OR (95% CI)††† 1.00 1.17 (0.79-1.72) 1.17 (0.79-1.73) 0.96 (0.62-1.48) 0.97 Yes (n = 4, 174) 425 (50.78%) 474 (47.93%) 583 (54.23%) 765 (60.09%) < 0.0001 Multivariate adjusted OR (95% CI)††† 1.00 1.02 (0.72-1.45) 1.18 (0.84-1.66) 1.36 (0.97-1.92) 0.04 Dyslipidemia No (n = 4, 829) 469 (30.67%) 412 (31.94%) 431 (37.19%) 374 (43.95%) < 0.0001 Multivariate adjusted OR (95% CI)†††† 1.00 1.14 (0.82-1.59) 1.14 (0.81-1.59) 1.30 (0.92-1.86) 0.17 Yes (n = 2, 861) 186 (42.76%) 265 (40.83%) 367 (47.97%) 546 (53.95%) < 0.0001 Multivariate adjusted OR (95% CI)†††† 1.00 0.81 (0.50-1.31) 1.12 (0.71-1.77) 1.17 (0.75-1.84) 0.15 Note. OR, odds ratio; CI, confidence interval; ASCVD, atherosclerotic cardiovascular diseases; †Multivariable model adjusted for education attainment, current smoking status, current alcohol consumption, MET-min/week, BMI, HbA1c, SBP, total cholesterol. ††Multivariable model adjusted for age, education attainment, current smoking status, current alcohol consumption, MET-min/week, HbA1c, SBP, total cholesterol. †††Multivariable model adjusted for age, education attainment, current smoking status, current alcohol consumption, MET-min/week, BMI, HbA1c, total cholesterol. ††††Multivariable model adjusted for age, education attainment, current smoking status, current alcohol consumption, MET-min/week, BMI, HbA1c, SBP. Significant data in bold. Endothelial dysfunction and oxidative stress in adipocytes are two potential mechanisms underlying the association between serum uric acid and cardiovascular risk. First, serum uric acid may harm the functions of platelets and endothelium[1]. Uric acid can induce oxidative stress, leading to attenuated nitric oxide bioavailability, which can promote proliferation of vascular smooth muscle[24]. Experimental studies in rats have reported that hyperuricemia induces endothelial dysfunction and that allopurinol improves endothelial function in patients with hyperuricemia, which supports the above mechanism[1]. Uric acid induces cellular proliferation, inflammation, oxidative stress, and activation of the local renin–angiotensin system in cultured vascular smooth muscle cells[1, 25, 26]. Microvascular changes still develop when blood pressure is controlled by a diuretic[1]. Furthermore, the mechanism of uric acid transport is still not completely understood. As the function of urate transport is essential for determining serum uric acid concentrations, further studies on the functional role of a uric acid transporter will provide a novel strategy to treat hyperuricemia-associated diseases[27, 28].
The main strength of our study was the large sample size, the exclusion of subjects with diabetes, and the gender specific analysis. Several limitations in our study should be mentioned. First, due to the cross-sectional design, no causal inferences can be drawn on the issue of serum uric acid and cardiovascular risks. Second, higher serum uric acid levels may indirectly contribute to increased cardiometabolic disease risk through a close association with established risk factors, such as older age, obesity, hypertension, dyslipidemia, dysglycemia, and chronic kidney disease. The exact mechanisms should be further investigated. Third, our study was conducted among a middle-aged and elderly Chinese population and should be carefully interpreted in other age and ethnical populations. Lastly, the information on cardiovascular diseases was collected through self-reported data, which might lead to inevitable recall bias.
To conclude, we found that serum uric acid was independently associated with an increased risk of obesity, hypertension, dyslipidemia, the 10-year Framingham risk for coronary heart disease, and the 10-year risk for ASCVD among the middle-aged and elderly Chinese population. As uric acid levels are effectively and safely modifiable with treatment, reducing serum uric acid might be preventive for cardiometabolic diseases and could be translated into large public heath gains. Further investigations are needed to confirm this association and the exact mechanisms.
doi: 10.3967/bes2018.013
Serum Uric Acid is Associated with the Predicted Risk of Prevalent Cardiovascular Disease in a Community-dwelling Population without Diabetes
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Abstract:
Objective To examine the association between serum uric acid levels and cardiovascular disease risk among individuals without diabetes. Methods We investigated the association between serum uric acid levels and the risk of prevalent cardiometabolic diseases, 10-year Framingham risk for coronary heart disease, and 10-year risk for atherosclerotic cardiovascular diseases (ASCVD) among 8, 252 participants aged ≥ 40 years without diabetes from Jiading district, Shanghai, China. Results Body mass index, waist circumference, blood glucose, glycated hemoglobin, blood pressure, and serum lipids increased progressively across the sex-specific quartiles of uric acid (all P trend < 0.05). Compared with individuals in the lowest quartile, those in the higher quartiles had a significantly higher prevalence of obesity, hypertension, and dyslipidemia (all P trend < 0.05). A fully adjusted logistic regression analysis revealed that individuals in the highest quartile had an increased risk of predicted cardiovascular disease compared with those in the lowest quartile of uric acid. The multivariate adjusted odds ratios (ORs)[95% confidence intervals (CIs)] for the highest quartiles for high Framingham risk were 3.00 (2.00-4.50) in men and 2.95 (1.08-8.43) in women. The multivariate adjusted ORs (95% CIs) for the highest quartile for high ASCVD risk were 1.93 (1.17-3.17) in men and 4.53 (2.57-7.98) in women. Conclusion Serum uric acid level is associated with an increased risk of prevalent obesity, hypertension, dyslipidemia, 10-year Framingham risk for coronary heart disease, and 10-year risk for ASCVD among Chinese adults without diabetes. -
Figure 1. Distribution of estimated 10-year risk for a first hard atherosclerotic cardiovascular diseases (ASCVD) event (A) and 10-year Framingham risk for coronary heart disease (B) in middle-aged and elderly Chinese adults without diabetes or CVD, stratified by sex and serum uric acid concentration groups (N = 7, 690).
Table 1. Characteristics of the Study Populations according to Serum Uric Acid Quartiles (N = 8, 252)
Characteristics UA (μmol/L) P for Trend Q1 Q2 Q3 Q4 Men Number/percentage, % 764 (25.0%) 762 (25.0%) 763 (25.0%) 762 (25.0%) Uric acid, μmol/L 258.5 (232.3-278.9) 319.8 (307.8-332.2) 371.2 (359.1-387.7) 451.5 (424.8-495.1) < 0.0001 Age, years 58.3 ± 9.2 57.0 ± 9.2 57.6 ± 9.1 58.4 ± 9.6 0.0081 High school education or above, % 175 (22.9%) 201 (26.4%) 193 (25.3%) 198 (26.0%) 0.72 Current smoker, % 454 (60.0%) 419 (55.7%) 426 (56.4%) 367 (48.9%) 0.0001 Current drinker, % 157 (20.8%) 188 (25.3%) 207 (27.5%) 223 (30.1%) 0.0001 Physically active during leisure time, % 105 (13.7%) 94 (12.3%) 104 (13.6%) 106 (13.9%) 0.93 BMI, kg/m2 23.9 ± 2.8 24.8 ± 3.0 25.5 ± 3.0 26.2 ± 3.0 < 0.0001 Waist circumference, cm 81.1 ± 7.7 84.0 ± 8.3 86.2 ± 8.0 88.4 ± 8.1 < 0.0001 SBP, mmHg 136.7 ± 18.4 138.6 ± 18.2 140.3 ± 18.6 141.1 ± 17.8 < 0.0001 DBP, mmHg 82.0 ± 10.3 84.0 ± 9.9 85.3 ± 10.0 86.0 ± 10.0 < 0.0001 FBG, mmol/L 5.1 ± 0.6 5.1 ± 0.6 5.1 ± 0.6 5.2 ± 0.6 0.0008 PBG, mmol/L 6.0 ± 1.8 6.3 ± 1.8 6.4 ± 1.8 6.9 ± 1.8 < 0.0001 HbA1c, % 5.5 (5.3-5.7) 5.5 (5.3-5.7) 5.5 (5.3-5.7) 5.6 (5.3-5.8) 0.0072 Total cholesterol, mg/dL 4.88 ± 0.82 5.08 ± 0.96 5.11 ± 0.84 5.23 ± 0.97 < 0.0001 Triglyceride, mg/dL 1.03 (0.77-1.41) 1.25 (0.95-1.73) 1.41 (1.02-1.98) 1.73 (1.22-2.50) < 0.0001 HDL-C, mg/dL 1.33 ± 0.31 1.25 ± 0.30 1.22 ± 0.29 1.19 ± 0.29 < 0.0001 LDL-C, mg/dL 2.85 ± 0.69 3.04 ± 0.76 3.06 ± 0.75 3.11 ± 0.86 < 0.0001 HOMA-IR 0.97 (0.56-1.38) 1.23 (0.83-1.81) 1.49 (0.96-2.14) 1.67 (1.10-2.44) < 0.0001 Women Number/percentage % 1301 (25.0%) 1300 (25.0%) 1301 (25.0%) 1299 (25.0%) Uric acid, μmol/L 183.0 (160.8-197.8) 232.30 (222.05-243.45) 277.4 (265.8-289.9) 347.8 (324.5-390.2) < 0.0001 Age, years 54.6 ± 8.8 56.1 ± 8.3 57.5 ± 8.8 59.7 ± 8.5 < 0.0001 High school education or above, % 295 (22.7%) 284 (21.9%) 281 (21.6%) 225 (17.3%) 0.0034 Current smoker, % 5 (0.4%) 4 (0.3%) 6 (0.5%) 9 (0.7%) 0.50 Current drinker, % 7 (0.6%) 9 (0.7%) 15 (1.2%) 10 (0.8%) 0.32 Physically active during leisure time, % 161 (12.4%) 203 (15.6%) 210 (16.1%) 209 (16.1%) 0.02 BMI, kg/m2 23.6 ± 3.0 24.4 ± 2.9 25.1 ± 3.2 26.1 ± 3.3 < 0.0001 Waist circumference, cm 76.5 ± 8.0 79.0 ± 7.4 80.9 ± 8.2 83.7 ± 8.3 < 0.0001 SBP, mmHg 133.6 ± 18.7 137.4 ± 19.4 139.5 ± 20.3 145.0 ± 20.3 < 0.0001 DBP, mmHg 79.6 ± 9.9 81.0 ± 9.9 82.0 ± 10.0 83.6 ± 10.3 < 0.0001 FBG, mmol/L 5.0 ± 0.5 5.1 ± 0.5 5.1 ± 0.6 5.2 ± 0.6 < 0.0001 PBG, mmol/L 6.4 ± 1.5 6.7 ± 1.6 6.9 ± 1.7 7.3 ± 1.7 < 0.0001 HbA1c, % 5.5 (5.3-5.7) 5.5 (5.3-5.7) 5.6 (5.4-5.8) 5.6 (5.4-5.9) < 0.0001 Total cholesterol, mg/dL 5.24 ± 0.96 5.41 ± 0.90 5.45 ± 1.03 5.67 ± 1.10 < 0.0001 Triglyceride, mg/dL 1.03 (0.78-1.41) 1.24 (0.93-1.74) 1.39 (1.03-1.90) 1.66 (1.25-2.36) < 0.0001 HDL-C, mg/dL 1.49 ± 0.33 1.41 ± 0.30 1.36 ± 0.30 1.30 ± 0.29 < 0.0001 LDL-C, mg/dL 3.08 ± 0.83 3.24 ± 0.80 3.29 ± 0.91 3.45 ± 0.92 < 0.0001 HOMA-IR 1.28 (0.89-1.73) 1.46 (1.02-2.01) 1.68 (1.17-2.38) 2.02 (1.42-2.92) < 0.0001 Note. UA, uric acid; BMI, body mass index; SBP, systolic blood pressure; DBP, diastolic blood pressure; FPG, fasting plasma glucose; PBG, postprandial blood glucose; HbA1c, hemoglobin A1; LDL-C, low density lipoprotein cholesterol; HDL-C, high density lipoprotein cholesterol. Table 2. Association between Serum Uric Acid Concentrations and Cardiovascular Risk Factors in Middle-aged and Elderly Chinese Adults without Diabetes (N = 8, 252)
Variables UA (μmol/L) P for Trend Q1 Q2 Q3 Q4 Obesity Men (n = 3, 051) Case percentage (%) 19 (2.49%) 37 (4.86%) 48 (6.29%) 69 (9.06%) < 0.0001 Age-adjusted OR (95% CI) 1.00 1.98 (1.13-3.47) 2.62 (1.52-4.50) 3.91 (2.33-6.56) < 0.0001 Multivariate adjusted OR (95% CI)* 1.00 1.88 (1.06-3.33) 2.34 (1.35-4.06) 3.42 (2.01-5.81) < 0.0001 Women (n = 5, 201) Case percentage (%) 34 (2.61%) 46 (3.54%) 76 (5.84%) 155 (11.93%) < 0.0001 Age-adjusted OR (95% CI) 1.00 1.36 (0.87-2.14) 2.29 (1.52-3.47) 4.98 (3.38-7.32) < 0.0001 Multivariate adjusted OR (95% CI)* 1.00 1.34 (0.85-2.12) 2.04 (1.33-3.13) 4.18 (2.80-6.24) < 0.0001 Hypertension Men (n = 3, 051) Case percentage (%) 390 (51.05%) 439 (57.61%) 464 (60.81%) 519 (68.11%) < 0.0001 Age-adjusted OR (95% CI) 1.00 1.44 (1.17-1.78) 1.60 (1.30-1.97) 2.16 (1.74-2.67) < 0.0001 Multivariate adjusted OR (95% CI)** 1.00 1.15 (0.92-1.43) 1.13 (0.90-1.41) 1.29 (1.02-1.63) 0.04 Women (n = 5, 201) Case percentage (%) 515 (39.58%) 640 (49.23%) 721 (55.42%) 920 (70.82%) < 0.0001 Age-adjusted OR (95% CI) 1.00 1.37 (1.17-1.62) 2.86 (2.42-3.40) 1.07 (1.06-1.08) < 0.0001 Multivariate adjusted OR (95% CI)** 1.00 1.16 (0.98-1.38) 1.30 (1.09-1.54) 1.96 (1.63-2.36) < 0.0001 Dyslipidemia Men (n = 3, 051) Case percentage (%) 188 (24.61%) 279 (36.61%) 330 (43.25%) 432 (56.69%) < 0.0001 Age-adjusted OR (95% CI) 1.00 1.72 (1.38-2.15) 2.32 (1.86-2.89) 4.11 (3.29-5.12) < 0.0001 Multivariate adjusted OR (95% CI)*** 1.00 1.49 (1.18-1.88) 1.89 (1.50-2.38) 3.16 (2.50-3.99) < 0.0001 Women (n = 5, 201) Case percentage (%) 273 (20.98%) 420 (32.31%) 491 (37.74%) 689 (53.04%) < 0.0001 Age-adjusted OR (95% CI) 1.00 1.75 (1.47-2.09) 2.17 (1.82-2.58) 3.88 (3.25-4.62) < 0.0001 Multivariate adjusted OR (95% CI)*** 1.00 1.66 (1.39-2.00) 1.99 (1.66-2.38) 3.23 (2.68-3.88) < 0.0001 Note. OR, odds ratio; CI, confidence interval; UA, uric acid; BMI, body mass index; *Multivariable model adjusted for age, education attainment, current smoking status, current alcohol consumption, MET-min/week, HbA1c, SBP, total cholesterol. **Multivariable model adjusted for age, education attainment, current smoking status, current alcohol consumption, MET-min/week, BMI, HbA1c, total cholesterol. ***Multivariable model adjusted for age, education attainment, current smoking status, current alcohol consumption, MET-min/week, BMI, HbA1c, SBP. Significant data in bold. Table 3. Association between Serum Uric Acid Levels and Cardiovascular Disease in Middle-aged and Elderly Chinese Adults without Diabetes
Variables UA (μmol/L) P for Trend Q1 Q2 Q3 Q4 Cardiovascular diseases (n = 8, 252) Men (n = 3, 051) Case percentage (%) 42 (5.50%) 45 (5.91%) 60 (7.86%) 74 (9.71%) 0.0003 Age-adjusted OR (95% CI) 1.00 1.22 (0.78-1.89) 1.60 (1.06-2.44) 1.85 (1.24-2.77) 0.001 Multivariate adjusted OR (95% CI)† 1.00 1.16 (0.74-1.82) 1.51 (0.99-2.33) 1.67 (1.09-2.55) 0.009 Women (n = 5, 201) Case percentage (%) 59 (4.53%) 78 (6.00%) 80 (6.15%) 124 (9.55%) Age-adjusted OR (95% CI) 1.00 1.25 (0.88-1.77) 1.14 (0.80-1.62) 1.61 (1.16-2.23) 0.007 Multivariate adjusted OR (95% CI)† 1.00 1.21 (0.84-1.72) 1.13 (0.79-1.62) 1.50 (1.06-2.12) 0.03 Framingham risk score > 20%††† (n = 7, 690) Men (n = 2, 830) Case percentage (%) 61 (8.45%) 78 (10.88%) 105 (14.94%) 132 (19.19%) < 0.0001 Age-adjusted OR (95% CI) 1.00 1.54 (1.10-2.18) 2.14 (1.54-2.98) 2.83 (2.01-3.98) < 0.0001 Multivariate adjusted OR (95% CI)† 1.00 1.39 (0.92-2.12) 2.05 (1.37-3.06) 3.00 (2.00-4.50) < 0.0001 Women (n = 4, 860) Case percentage (%) 6 (0.49%) 5 (0.42%) 7 (0.58%) 29 (2.39%) < 0.0001 Age-adjusted OR (95% CI) 1.00 0.39 (0.11-1.41) 1.07 (0.42-2.74) 4.73 (1.70-11.25) 0.0005 Multivariate adjusted OR (95% CI)† 1.00 0.44 (0.10-1.83) 1.01 (0.33-1.75) 2.95 (1.08-8.43) 0.01 ASCVD risk score ≥ 7.5%†† (n = 7, 690) Men (n = 2, 830) Case percentage (%) 484 (67.04%) 487 (67.92%) 511 (72.69%) 509 (73.98%) 0.0004 Age-adjusted OR (95% CI) 1.00 1.49 (1.11-2.00) 1.98 (1.46-2.69) 2.08 (1.52-2.84) < 0.0001 Multivariate adjusted OR (95% CI)† 1.00 1.52 (0.97-2.41) 1.87 (1.17-2.99) 1.93 (1.17-3.17) 0.005 Women (n = 4, 860) Case percentage (%) 171 (13.77%) 190 (15.55%) 287 (23.51%) 411 (34.98%) < 0.0001 Age-adjusted OR (95% CI) 1.00 1.41 (0.97-2.04) 2.62 (1.83-3.74) 5.40 (3.71-7.87) < 0.0001 Multivariate adjusted OR (95% CI)† 1.00 1.06 (0.58-1.91) 2.48 (1.39-4.42) 4.53 (2.57-7.98) < 0.0001 Note. OR, odds ratio; CI, confidence interval; CVD, cardiovascular diseases; ASCVD, atherosclerotic cardiovascular diseases; HOMA-IR, homeostasis model assessment of insulin resistance. †Multivariable model adjusted for age, education attainment, current smoking status, current alcohol consumption, MET-min/week, BMI, HbA1c, SBP, total cholesterol. ††Analysis was carried out in participants ages 40-79 years old, free of CVD and diabetes (N = 7, 690) and individuals with ASCVD score ≥ 7.5% were identified as at high risks for 10-year ASCVD. †††Analysis was carried out in participants ages 40-79 years old, free of CVD and diabetes (n = 7, 690), and Framingham risk score > 20% were identified as at high risks for 10-year coronary heart disease. Significant data in bold. Table S1. Subgroup Analysis of the Association between Serum Uric Acid Levels and Cardiovascular Diseases in Middle-Aged and Elderly Chinese Adults without Diabetes
Variables UA (μmol/L) P for Trend Q1 Q2 Q3 Q4 Cardiovascular diseases (n = 8, 252) Age < 60 y (n = 5, 247) 40 (2.84%) 57 (4.07%) 36 (2.79%) 65 (5.66%) 0.002 Multivariate adjusted OR (95% CI)† 1.00 1.33 (0.87-2.02) 0.91 (0.57-1.45) 1.72 (1.12-2.66) 0.06 ≥ 60 y (n = 2, 641) 61 (9.28%) 66 (9.98%) 104 (13.42%) 133 (14.58%) 0.0001 Multivariate adjusted OR (95% CI)† 1.00 1.03 (0.71-1.49) 1.44 (1.02-2.02) 1.45 (1.03-2.04) 0.009 Obesity No (n = 7, 768) 97 (4.82%) 112 (5.66%) 127 (6.55%) 163 (8.87%) < 0.0001 Multivariate adjusted OR (95% CI)†† 1.00 1.13 (0.85-1.50) 1.22 (0.92-1.62) 1.43 (1.09-1.89) 0.009 Yes (n = 484) 4 (7.55%) 11 (13.25%) 13 (10.48%) 35 (15.63%) 0.07 Multivariate adjusted OR (95% CI)†† 1.00 2.05 (0.58-7.20) 1.53 (0.45-5.22) 2.13 (0.68-6.71) 0.29 Hypertension No (n = 3, 644) 33 (2.84%) 33 (3.36%) 30 (3.41%) 32 (5.14%) 0.01 Multivariate adjusted OR (95% CI)††† 1.00 1.12 (0.68-1.86) 1.13 (0.68-1.90) 1.68 (0.99-2.85) 0.08 Yes (n = 4, 608) 68 (7.51%) 90 (8.34%) 110 (9.28%) 166 (11.54%) 0.0003 Multivariate adjusted OR (95% CI)††† 1.00 1.16 (0.83-1.63) 1.18 (0.85-1.64) 1.28 (0.93-1.75) 0.15 Dyslipidemia No (n = 5, 150) 75 (4.68%) 73 (5.36%) 84 (6.76%) 89 (9.47%) < 0.0001 Multivariate adjusted OR (95% CI)†††† 1.00 1.09 (0.77-1.53) 1.27 (0.91-1.77) 1.56 (1.12-2.19) 0.006 Yes (n = 3, 102) 26 (5.64%) 50 (7.15%) 56 (6.82%) 109 (9.72%) 0.002 Multivariate adjusted OR (95% CI)†††† 1.00 1.27 (0.77-2.10) 1.10 (0.67-1.81) 1.28 (0.80-2.04) 0.45 Framingham risk score > 20% (n = 7, 690) Age < 60 y (n = 5, 049) 31 (2.27%) 41 (3.05%) 63 (5.03%) 51 (4.70%) < 0.0001 Multivariate adjusted OR (95% CI)† 1.00 0.96 (0.54-1.70) 1.75 (1.01-3.01) 1.25 (0.70-2.23) < 0.0001 ≥ 60 y (n = 2, 641) 36 (6.04%) 42 (7.06%) 49 (7.30%) 110 (14.12%) < 0.0001 Multivariate adjusted OR (95% CI)† 1.00 1.06 (0.63-1.79) 1.01 (0.61-1.66) 1.97 (1.23-3.15) 0.01 Obesity No (n = 7, 269) 64 (3.34%) 80 (4.28%) 105 (5.79%) 147 (8.78%) < 0.0001 Multivariate adjusted OR (95% CI)†† 1.00 1.32 (0.87-2.00) 1.59 (1.07-2.37) 2.12 (1.43-3.14) < 0.0001 Yes (n = 421) 3 (6.12%) 3 (4.17%) 7 (6.31%) 14 (7.41%) 0.23 Multivariate adjusted OR (95% CI)†† 1.00 0.59 (0.07-4.77) 0.89 (0.14-5.62) 1.13 (0.21-6.09) 0.62 Hypertension No (n = 3, 516) 9 (0.80%) 8 (0.84%) 17 (2.00%) 7 (1.19%) 0.05 Multivariate adjusted OR (95% CI)††† 1.00 0.82 (0.28-2.38) 1.49 (0.58-3.84) 0.71 (0.23-2.20) 0.92 Yes (n = 4, 174) 58 (6.93%) 75 (7.58%) 95 (8.84%) 154 (12.10%) < 0.0001 Multivariate adjusted OR (95% CI)††† 1.00 1.39 (0.90-2.17) 1.56 (1.02-2.38) 1.98 (1.31-3.00) 0.001 Dyslipidemia No (n = 4, 829) 28 (1.83%) 32 (2.48%) 32 (2.76%) 30 (3.53%) 0.01 Multivariate adjusted OR (95% CI)†††† 1.00 1.75 (0.95-3.20) 1.65 (0.90-3.04) 1.98 (1.04-3.77) 0.05 Yes (n = 2, 861) 39 (8.97%) 51 (7.86%) 80 (10.46%) 131 (12.94%) 0.001 Multivariate adjusted OR (95% CI)†††† 1.00 0.88 (0.50-1.54) 1.25 (0.74-2.10) 1.61 (0.97-2.66) 0.01 ASCVD risk score ≥ 7.5% (n = 7, 690) Age < 60 y (n = 5, 049) 204 (14.91%) 248 (18.45%) 279 (22.27%) 270 (24.91%) < 0.0001 Multivariate adjusted OR (95% CI)† 1.00 1.09 (0.81-1.47) 1.26 (0.94-1.70) 1.24 (0.91-1.69) 0.11 ≥ 60 y (n = 2, 641) 451 (75.67%) 429 (72.10%) 519 (77.35%) 650 (83.44%) < 0.0001 Multivariate adjusted OR (95% CI)† 1.00 0.77 (0.57-1.06) 1.00 (0.73-1.37) 1.43 (1.04-1.98) 0.007 Obesity No (n = 7, 269) 639 (33.21%) 644 (34.49%) 750 (41.37%) 825 (49.28%) < 0.0001 Multivariate adjusted OR (95% CI)†† 1.00 1.07 (0.82-1.40) 1.33 (1.02-1.73) 1.53 (1.17-2.00) 0.001 Yes (n = 421) 19 (38.78%) 33 (45.83%) 48 (43.24%) 95 (50.26%) 0.08 Multivariate adjusted OR (95% CI)†† 1.00 1.84 (0.57-5.94) 1.74 (0.57-5.28) 1.19 (0.41-3.43) 0.09 Hypertension No (n = 3, 516) 230 (20.41%) 203 (21.37%) 215 (25.32%) 155 (26.27%) 0.001 Multivariate adjusted OR (95% CI)††† 1.00 1.17 (0.79-1.72) 1.17 (0.79-1.73) 0.96 (0.62-1.48) 0.97 Yes (n = 4, 174) 425 (50.78%) 474 (47.93%) 583 (54.23%) 765 (60.09%) < 0.0001 Multivariate adjusted OR (95% CI)††† 1.00 1.02 (0.72-1.45) 1.18 (0.84-1.66) 1.36 (0.97-1.92) 0.04 Dyslipidemia No (n = 4, 829) 469 (30.67%) 412 (31.94%) 431 (37.19%) 374 (43.95%) < 0.0001 Multivariate adjusted OR (95% CI)†††† 1.00 1.14 (0.82-1.59) 1.14 (0.81-1.59) 1.30 (0.92-1.86) 0.17 Yes (n = 2, 861) 186 (42.76%) 265 (40.83%) 367 (47.97%) 546 (53.95%) < 0.0001 Multivariate adjusted OR (95% CI)†††† 1.00 0.81 (0.50-1.31) 1.12 (0.71-1.77) 1.17 (0.75-1.84) 0.15 Note. OR, odds ratio; CI, confidence interval; ASCVD, atherosclerotic cardiovascular diseases; †Multivariable model adjusted for education attainment, current smoking status, current alcohol consumption, MET-min/week, BMI, HbA1c, SBP, total cholesterol. ††Multivariable model adjusted for age, education attainment, current smoking status, current alcohol consumption, MET-min/week, HbA1c, SBP, total cholesterol. †††Multivariable model adjusted for age, education attainment, current smoking status, current alcohol consumption, MET-min/week, BMI, HbA1c, total cholesterol. ††††Multivariable model adjusted for age, education attainment, current smoking status, current alcohol consumption, MET-min/week, BMI, HbA1c, SBP. Significant data in bold. -
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